High‐resolution time‐resolved imaging of in vitro Arabidopsis rosette growth

Although quantitative characterization of growth phenotypes is of key importance for the understanding of essential networks driving plant growth, the majority of growth‐related genes are still being identified based on qualitative visual observations and/or single‐endpoint quantitative measurements...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:The Plant journal : for cell and molecular biology 2014-10, Vol.80 (1), p.172-184
Hauptverfasser: Dhondt, Stijn, Gonzalez, Nathalie, Blomme, Jonas, De Milde, Liesbeth, Van Daele, Twiggy, Van Akoleyen, Dirk, Storme, Veronique, Coppens, Frederik, T.S. Beemster, Gerrit, Inzé, Dirk
Format: Artikel
Sprache:eng
Schlagworte:
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
container_end_page 184
container_issue 1
container_start_page 172
container_title The Plant journal : for cell and molecular biology
container_volume 80
creator Dhondt, Stijn
Gonzalez, Nathalie
Blomme, Jonas
De Milde, Liesbeth
Van Daele, Twiggy
Van Akoleyen, Dirk
Storme, Veronique
Coppens, Frederik
T.S. Beemster, Gerrit
Inzé, Dirk
description Although quantitative characterization of growth phenotypes is of key importance for the understanding of essential networks driving plant growth, the majority of growth‐related genes are still being identified based on qualitative visual observations and/or single‐endpoint quantitative measurements. We developed an in vitro growth imaging system (IGIS) to perform time‐resolved analysis of rosette growth. In this system, Arabidopsis plants are grown in Petri dishes mounted on a rotating disk, and images of each plate are taken on an hourly basis. Automated image analysis was developed in order to obtain several growth‐related parameters, such as projected rosette area, rosette relative growth rate, compactness and stockiness, over time. To illustrate the use of the platform and the resulting data, we present the results for the growth response of Col–0 plants subjected to three mild stress conditions. Although the reduction in rosette area was relatively similar at 19 days after stratification, the time‐lapse analysis demonstrated that plants react differently to salt, osmotic and oxidative stress. The rosette area was altered at various time points during development, and leaf movement and shape parameters were also affected differently. We also used the IGIS to analyze in detail the growth behavior of mutants with enhanced leaf size. Analysis of several growth‐related parameters over time in these mutants revealed several specificities in growth behavior, underlining the high complexity of leaf growth coordination. These results demonstrate that time‐resolved imaging of in vitro rosette growth generates a better understanding of growth phenotypes than endpoint measurements.
doi_str_mv 10.1111/tpj.12610
format Article
fullrecord <record><control><sourceid>proquest_hal_p</sourceid><recordid>TN_cdi_hal_primary_oai_HAL_hal_01601536v1</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>3437247231</sourcerecordid><originalsourceid>FETCH-LOGICAL-c5820-500a55d03b76bbc7100f92bddc757afae861e59c70acc4060567d1e5141802b93</originalsourceid><addsrcrecordid>eNp1kc1u1DAUhS0EotPCgheASGzKIu29_k2WowoY0EhUopXYWU7iZDzKxIOdTNUdj8Az8iR4mE6RkLgbS0efz71Hh5BXCBeY5nLcri-QSoQnZIZMipwh-_aUzKCUkCuO9IScxrgGQMUkf05OqACOUIgZuV64bvXrx89go--n0fkhG93GHpWdbTK3MZ0busy3mRuynRuDz-bBVK7x2-hiFny042izLvi7cfWCPGtNH-3Lh_eM3H54f3O1yJdfPn66mi_zWhQUcgFghGiAVUpWVa0QoC1p1TS1Esq0xhYSrShrBaauOUgQUjVJQY4F0KpkZ-TdwXdler0N6chwr71xejFf6r0GKAEFkztM7PmB3Qb_fbJx1BsXa9v3ZrB-ihqF5BLKkvOEvv0HXfspDCnJnmJc8ULwv8vrFD4G2z5egKD3lehUif5TSWJfPzhO1cY2j-SxgwRcHoA719v7_zvpm-vPR8s3hx-t8dp0wUV9-5WmtABAQVLGfgNvPZ6g</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1563474854</pqid></control><display><type>article</type><title>High‐resolution time‐resolved imaging of in vitro Arabidopsis rosette growth</title><source>Wiley Free Content</source><source>MEDLINE</source><source>IngentaConnect Free/Open Access Journals</source><source>Wiley Online Library Journals Frontfile Complete</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><creator>Dhondt, Stijn ; Gonzalez, Nathalie ; Blomme, Jonas ; De Milde, Liesbeth ; Van Daele, Twiggy ; Van Akoleyen, Dirk ; Storme, Veronique ; Coppens, Frederik ; T.S. Beemster, Gerrit ; Inzé, Dirk</creator><creatorcontrib>Dhondt, Stijn ; Gonzalez, Nathalie ; Blomme, Jonas ; De Milde, Liesbeth ; Van Daele, Twiggy ; Van Akoleyen, Dirk ; Storme, Veronique ; Coppens, Frederik ; T.S. Beemster, Gerrit ; Inzé, Dirk</creatorcontrib><description>Although quantitative characterization of growth phenotypes is of key importance for the understanding of essential networks driving plant growth, the majority of growth‐related genes are still being identified based on qualitative visual observations and/or single‐endpoint quantitative measurements. We developed an in vitro growth imaging system (IGIS) to perform time‐resolved analysis of rosette growth. In this system, Arabidopsis plants are grown in Petri dishes mounted on a rotating disk, and images of each plate are taken on an hourly basis. Automated image analysis was developed in order to obtain several growth‐related parameters, such as projected rosette area, rosette relative growth rate, compactness and stockiness, over time. To illustrate the use of the platform and the resulting data, we present the results for the growth response of Col–0 plants subjected to three mild stress conditions. Although the reduction in rosette area was relatively similar at 19 days after stratification, the time‐lapse analysis demonstrated that plants react differently to salt, osmotic and oxidative stress. The rosette area was altered at various time points during development, and leaf movement and shape parameters were also affected differently. We also used the IGIS to analyze in detail the growth behavior of mutants with enhanced leaf size. Analysis of several growth‐related parameters over time in these mutants revealed several specificities in growth behavior, underlining the high complexity of leaf growth coordination. These results demonstrate that time‐resolved imaging of in vitro rosette growth generates a better understanding of growth phenotypes than endpoint measurements.</description><identifier>ISSN: 0960-7412</identifier><identifier>EISSN: 1365-313X</identifier><identifier>DOI: 10.1111/tpj.12610</identifier><identifier>PMID: 25041085</identifier><language>eng</language><publisher>England: Blackwell Scientific Publishers and BIOS Scientific Publishers in association with the Society for Experimental Biology</publisher><subject>Arabidopsis ; Arabidopsis - genetics ; Arabidopsis - growth &amp; development ; Arabidopsis - radiation effects ; Arabidopsis thaliana ; genes ; Genotype ; Genotype &amp; phenotype ; growth dynamics ; image analysis ; Image Processing, Computer-Assisted - instrumentation ; Image Processing, Computer-Assisted - methods ; imaging ; leaf movement ; leaves ; Life Sciences ; Light ; mutants ; Mutation ; oxidative stress ; Phenotype ; phenotyping platform ; Plant biology ; Plant growth ; Plant Leaves - genetics ; Plant Leaves - growth &amp; development ; Plant Leaves - radiation effects ; Plants, Genetically Modified ; rosette ; Seedlings - genetics ; Seedlings - growth &amp; development ; Seedlings - radiation effects ; technical advance ; Time Factors</subject><ispartof>The Plant journal : for cell and molecular biology, 2014-10, Vol.80 (1), p.172-184</ispartof><rights>2014 The Authors The Plant Journal © 2014 John Wiley &amp; Sons Ltd</rights><rights>2014 The Authors The Plant Journal © 2014 John Wiley &amp; Sons Ltd.</rights><rights>Copyright © 2014 John Wiley &amp; Sons Ltd and the Society for Experimental Biology</rights><rights>Distributed under a Creative Commons Attribution 4.0 International License</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5820-500a55d03b76bbc7100f92bddc757afae861e59c70acc4060567d1e5141802b93</citedby><cites>FETCH-LOGICAL-c5820-500a55d03b76bbc7100f92bddc757afae861e59c70acc4060567d1e5141802b93</cites><orcidid>0000-0001-6565-5145 ; 0000-0002-3946-1758</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Ftpj.12610$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Ftpj.12610$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>230,314,776,780,881,1411,1427,27903,27904,45553,45554,46387,46811</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25041085$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://hal.science/hal-01601536$$DView record in HAL$$Hfree_for_read</backlink></links><search><creatorcontrib>Dhondt, Stijn</creatorcontrib><creatorcontrib>Gonzalez, Nathalie</creatorcontrib><creatorcontrib>Blomme, Jonas</creatorcontrib><creatorcontrib>De Milde, Liesbeth</creatorcontrib><creatorcontrib>Van Daele, Twiggy</creatorcontrib><creatorcontrib>Van Akoleyen, Dirk</creatorcontrib><creatorcontrib>Storme, Veronique</creatorcontrib><creatorcontrib>Coppens, Frederik</creatorcontrib><creatorcontrib>T.S. Beemster, Gerrit</creatorcontrib><creatorcontrib>Inzé, Dirk</creatorcontrib><title>High‐resolution time‐resolved imaging of in vitro Arabidopsis rosette growth</title><title>The Plant journal : for cell and molecular biology</title><addtitle>Plant J</addtitle><description>Although quantitative characterization of growth phenotypes is of key importance for the understanding of essential networks driving plant growth, the majority of growth‐related genes are still being identified based on qualitative visual observations and/or single‐endpoint quantitative measurements. We developed an in vitro growth imaging system (IGIS) to perform time‐resolved analysis of rosette growth. In this system, Arabidopsis plants are grown in Petri dishes mounted on a rotating disk, and images of each plate are taken on an hourly basis. Automated image analysis was developed in order to obtain several growth‐related parameters, such as projected rosette area, rosette relative growth rate, compactness and stockiness, over time. To illustrate the use of the platform and the resulting data, we present the results for the growth response of Col–0 plants subjected to three mild stress conditions. Although the reduction in rosette area was relatively similar at 19 days after stratification, the time‐lapse analysis demonstrated that plants react differently to salt, osmotic and oxidative stress. The rosette area was altered at various time points during development, and leaf movement and shape parameters were also affected differently. We also used the IGIS to analyze in detail the growth behavior of mutants with enhanced leaf size. Analysis of several growth‐related parameters over time in these mutants revealed several specificities in growth behavior, underlining the high complexity of leaf growth coordination. These results demonstrate that time‐resolved imaging of in vitro rosette growth generates a better understanding of growth phenotypes than endpoint measurements.</description><subject>Arabidopsis</subject><subject>Arabidopsis - genetics</subject><subject>Arabidopsis - growth &amp; development</subject><subject>Arabidopsis - radiation effects</subject><subject>Arabidopsis thaliana</subject><subject>genes</subject><subject>Genotype</subject><subject>Genotype &amp; phenotype</subject><subject>growth dynamics</subject><subject>image analysis</subject><subject>Image Processing, Computer-Assisted - instrumentation</subject><subject>Image Processing, Computer-Assisted - methods</subject><subject>imaging</subject><subject>leaf movement</subject><subject>leaves</subject><subject>Life Sciences</subject><subject>Light</subject><subject>mutants</subject><subject>Mutation</subject><subject>oxidative stress</subject><subject>Phenotype</subject><subject>phenotyping platform</subject><subject>Plant biology</subject><subject>Plant growth</subject><subject>Plant Leaves - genetics</subject><subject>Plant Leaves - growth &amp; development</subject><subject>Plant Leaves - radiation effects</subject><subject>Plants, Genetically Modified</subject><subject>rosette</subject><subject>Seedlings - genetics</subject><subject>Seedlings - growth &amp; development</subject><subject>Seedlings - radiation effects</subject><subject>technical advance</subject><subject>Time Factors</subject><issn>0960-7412</issn><issn>1365-313X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kc1u1DAUhS0EotPCgheASGzKIu29_k2WowoY0EhUopXYWU7iZDzKxIOdTNUdj8Az8iR4mE6RkLgbS0efz71Hh5BXCBeY5nLcri-QSoQnZIZMipwh-_aUzKCUkCuO9IScxrgGQMUkf05OqACOUIgZuV64bvXrx89go--n0fkhG93GHpWdbTK3MZ0busy3mRuynRuDz-bBVK7x2-hiFny042izLvi7cfWCPGtNH-3Lh_eM3H54f3O1yJdfPn66mi_zWhQUcgFghGiAVUpWVa0QoC1p1TS1Esq0xhYSrShrBaauOUgQUjVJQY4F0KpkZ-TdwXdler0N6chwr71xejFf6r0GKAEFkztM7PmB3Qb_fbJx1BsXa9v3ZrB-ihqF5BLKkvOEvv0HXfspDCnJnmJc8ULwv8vrFD4G2z5egKD3lehUif5TSWJfPzhO1cY2j-SxgwRcHoA719v7_zvpm-vPR8s3hx-t8dp0wUV9-5WmtABAQVLGfgNvPZ6g</recordid><startdate>201410</startdate><enddate>201410</enddate><creator>Dhondt, Stijn</creator><creator>Gonzalez, Nathalie</creator><creator>Blomme, Jonas</creator><creator>De Milde, Liesbeth</creator><creator>Van Daele, Twiggy</creator><creator>Van Akoleyen, Dirk</creator><creator>Storme, Veronique</creator><creator>Coppens, Frederik</creator><creator>T.S. Beemster, Gerrit</creator><creator>Inzé, Dirk</creator><general>Blackwell Scientific Publishers and BIOS Scientific Publishers in association with the Society for Experimental Biology</general><general>Blackwell Publishing Ltd</general><general>Wiley</general><scope>FBQ</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QO</scope><scope>7QP</scope><scope>7QR</scope><scope>7TM</scope><scope>8FD</scope><scope>FR3</scope><scope>M7N</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><scope>1XC</scope><orcidid>https://orcid.org/0000-0001-6565-5145</orcidid><orcidid>https://orcid.org/0000-0002-3946-1758</orcidid></search><sort><creationdate>201410</creationdate><title>High‐resolution time‐resolved imaging of in vitro Arabidopsis rosette growth</title><author>Dhondt, Stijn ; Gonzalez, Nathalie ; Blomme, Jonas ; De Milde, Liesbeth ; Van Daele, Twiggy ; Van Akoleyen, Dirk ; Storme, Veronique ; Coppens, Frederik ; T.S. Beemster, Gerrit ; Inzé, Dirk</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5820-500a55d03b76bbc7100f92bddc757afae861e59c70acc4060567d1e5141802b93</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Arabidopsis</topic><topic>Arabidopsis - genetics</topic><topic>Arabidopsis - growth &amp; development</topic><topic>Arabidopsis - radiation effects</topic><topic>Arabidopsis thaliana</topic><topic>genes</topic><topic>Genotype</topic><topic>Genotype &amp; phenotype</topic><topic>growth dynamics</topic><topic>image analysis</topic><topic>Image Processing, Computer-Assisted - instrumentation</topic><topic>Image Processing, Computer-Assisted - methods</topic><topic>imaging</topic><topic>leaf movement</topic><topic>leaves</topic><topic>Life Sciences</topic><topic>Light</topic><topic>mutants</topic><topic>Mutation</topic><topic>oxidative stress</topic><topic>Phenotype</topic><topic>phenotyping platform</topic><topic>Plant biology</topic><topic>Plant growth</topic><topic>Plant Leaves - genetics</topic><topic>Plant Leaves - growth &amp; development</topic><topic>Plant Leaves - radiation effects</topic><topic>Plants, Genetically Modified</topic><topic>rosette</topic><topic>Seedlings - genetics</topic><topic>Seedlings - growth &amp; development</topic><topic>Seedlings - radiation effects</topic><topic>technical advance</topic><topic>Time Factors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Dhondt, Stijn</creatorcontrib><creatorcontrib>Gonzalez, Nathalie</creatorcontrib><creatorcontrib>Blomme, Jonas</creatorcontrib><creatorcontrib>De Milde, Liesbeth</creatorcontrib><creatorcontrib>Van Daele, Twiggy</creatorcontrib><creatorcontrib>Van Akoleyen, Dirk</creatorcontrib><creatorcontrib>Storme, Veronique</creatorcontrib><creatorcontrib>Coppens, Frederik</creatorcontrib><creatorcontrib>T.S. Beemster, Gerrit</creatorcontrib><creatorcontrib>Inzé, Dirk</creatorcontrib><collection>AGRIS</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Biotechnology Research Abstracts</collection><collection>Calcium &amp; Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>Hyper Article en Ligne (HAL)</collection><jtitle>The Plant journal : for cell and molecular biology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Dhondt, Stijn</au><au>Gonzalez, Nathalie</au><au>Blomme, Jonas</au><au>De Milde, Liesbeth</au><au>Van Daele, Twiggy</au><au>Van Akoleyen, Dirk</au><au>Storme, Veronique</au><au>Coppens, Frederik</au><au>T.S. Beemster, Gerrit</au><au>Inzé, Dirk</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>High‐resolution time‐resolved imaging of in vitro Arabidopsis rosette growth</atitle><jtitle>The Plant journal : for cell and molecular biology</jtitle><addtitle>Plant J</addtitle><date>2014-10</date><risdate>2014</risdate><volume>80</volume><issue>1</issue><spage>172</spage><epage>184</epage><pages>172-184</pages><issn>0960-7412</issn><eissn>1365-313X</eissn><abstract>Although quantitative characterization of growth phenotypes is of key importance for the understanding of essential networks driving plant growth, the majority of growth‐related genes are still being identified based on qualitative visual observations and/or single‐endpoint quantitative measurements. We developed an in vitro growth imaging system (IGIS) to perform time‐resolved analysis of rosette growth. In this system, Arabidopsis plants are grown in Petri dishes mounted on a rotating disk, and images of each plate are taken on an hourly basis. Automated image analysis was developed in order to obtain several growth‐related parameters, such as projected rosette area, rosette relative growth rate, compactness and stockiness, over time. To illustrate the use of the platform and the resulting data, we present the results for the growth response of Col–0 plants subjected to three mild stress conditions. Although the reduction in rosette area was relatively similar at 19 days after stratification, the time‐lapse analysis demonstrated that plants react differently to salt, osmotic and oxidative stress. The rosette area was altered at various time points during development, and leaf movement and shape parameters were also affected differently. We also used the IGIS to analyze in detail the growth behavior of mutants with enhanced leaf size. Analysis of several growth‐related parameters over time in these mutants revealed several specificities in growth behavior, underlining the high complexity of leaf growth coordination. These results demonstrate that time‐resolved imaging of in vitro rosette growth generates a better understanding of growth phenotypes than endpoint measurements.</abstract><cop>England</cop><pub>Blackwell Scientific Publishers and BIOS Scientific Publishers in association with the Society for Experimental Biology</pub><pmid>25041085</pmid><doi>10.1111/tpj.12610</doi><tpages>13</tpages><orcidid>https://orcid.org/0000-0001-6565-5145</orcidid><orcidid>https://orcid.org/0000-0002-3946-1758</orcidid><oa>free_for_read</oa></addata></record>
fulltext fulltext
identifier ISSN: 0960-7412
ispartof The Plant journal : for cell and molecular biology, 2014-10, Vol.80 (1), p.172-184
issn 0960-7412
1365-313X
language eng
recordid cdi_hal_primary_oai_HAL_hal_01601536v1
source Wiley Free Content; MEDLINE; IngentaConnect Free/Open Access Journals; Wiley Online Library Journals Frontfile Complete; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals
subjects Arabidopsis
Arabidopsis - genetics
Arabidopsis - growth & development
Arabidopsis - radiation effects
Arabidopsis thaliana
genes
Genotype
Genotype & phenotype
growth dynamics
image analysis
Image Processing, Computer-Assisted - instrumentation
Image Processing, Computer-Assisted - methods
imaging
leaf movement
leaves
Life Sciences
Light
mutants
Mutation
oxidative stress
Phenotype
phenotyping platform
Plant biology
Plant growth
Plant Leaves - genetics
Plant Leaves - growth & development
Plant Leaves - radiation effects
Plants, Genetically Modified
rosette
Seedlings - genetics
Seedlings - growth & development
Seedlings - radiation effects
technical advance
Time Factors
title High‐resolution time‐resolved imaging of in vitro Arabidopsis rosette growth
url https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-27T14%3A25%3A38IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_hal_p&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=High%E2%80%90resolution%20time%E2%80%90resolved%20imaging%20of%20in%20vitro%20Arabidopsis%20rosette%20growth&rft.jtitle=The%20Plant%20journal%20:%20for%20cell%20and%20molecular%20biology&rft.au=Dhondt,%20Stijn&rft.date=2014-10&rft.volume=80&rft.issue=1&rft.spage=172&rft.epage=184&rft.pages=172-184&rft.issn=0960-7412&rft.eissn=1365-313X&rft_id=info:doi/10.1111/tpj.12610&rft_dat=%3Cproquest_hal_p%3E3437247231%3C/proquest_hal_p%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1563474854&rft_id=info:pmid/25041085&rfr_iscdi=true